Lactate transporters in the rat barrel cortex sustain whisker-dependent BOLD fMRI signal and behavioral performance.

Lactate is an efficient neuronal energy source, even in presence of glucose. However, the importance of lactate shuttling between astrocytes and neurons for brain activation and function remains to be established. For this purpose, metabolic and hemodynamic responses to sensory stimulation have been measured by functional magnetic resonance spectroscopy and blood oxygen level-dependent (BOLD) fMRI after down-regulation of either neuronal MCT2 or astroglial MCT4 in the rat barrel cortex. Results show that the lactate rise in the barrel cortex upon whisker stimulation is abolished when either transporter is down-regulated. Under the same paradigm, the BOLD response is prevented in all MCT2 down-regulated rats, while about half of the MCT4 down-regulated rats exhibited a loss of the BOLD response. Interestingly, MCT4 down-regulated animals showing no BOLD response were rescued by peripheral lactate infusion, while this treatment had no effect on MCT2 down-regulated rats. When animals were tested in a novel object recognition task, MCT2 down-regulated animals were impaired in the textured but not in the visual version of the task. For MCT4 down-regulated animals, while all animal succeeded in the visual task, half of them exhibited a deficit in the textured task, a similar segregation into two groups as observed for BOLD experiments. Our data demonstrate that lactate shuttling between astrocytes and neurons is essential to give rise to both neurometabolic and neurovascular couplings, which form the basis for the detection of brain activation by functional brain imaging techniques. Moreover, our results establish that this metabolic cooperation is required to sustain behavioral performance based on cortical activation.

The costs of coping: Different strategies to deal with social defeat stress might come with distinct immunologic, neuroplastic, and oxidative stress consequences in male Wistar rats.

The impact of stress on health and well-being is determined by the ability of an individual to cope with challenges imposed by the stressor. Animals exposed to social defeat stress show different patterns of response during confrontations, leading to distinct stress-induced consequences. Using an established resident-intruder paradigm, we explored the outcomes of adopting active or passive coping strategies during a social defeat protocol over peripheral and central nervous system (CNS) levels of inflammatory cytokines, growth factors, glucocorticoid, and oxidative stress markers in male Wistar rats. Animals that presented short latency to assume a defeated posture during confrontation-considered as susceptible to stress-exhibited increased levels of brain-derived neurotrophic factor (BDNF) in the amygdala (AMY) and in the bed nucleus of the stria terminalis (BNST), and decreased lipid peroxidation in the CNS, suggesting changes in antioxidative defenses as well as stress-induced neuroadaptations. On the other hand, animals with longer latencies to assume a submissive posture-considered to be resilient to stress-presented lower levels of CNS BDNF compared to short-latency animals and decreased enzymatic antioxidant defenses in the CNS in comparison to controls, which might indicate an increased risk of central oxidative damage. From the results, behavioral reactivity cannot be considered a predictor of success in responding to stress; however, the findings of this study reinforce the idea that exposure to stress has no predetermined negative effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cofilin/actin rod formation by dysregulation of cofilin-1 activity as a central initial step in neurodegeneration.

Cofilin-1 protein, which main function is to regulate actin cytoskeleton dynamics, appears to be involved with many steps in the neurotoxicity processes found in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). As the dynamics of actin filaments play a major role in several cellular processes, the primary involvement of cofilin-1 dysfunctions in the pathophysiology of these disorders may be related to a cytoskeleton stress. However, recently cofilin-1 has also been related to other biological processes such as cell death by apoptosis. In both cases, ATP depletion associated with the presence of reactive species and other stressors regulate cofilin-1 by inducing the formation of aggregates composed primarily by actin and cofilin-1, known as cofilin/actin rods. These structures seem to be formed initially as a neuroprotective response to mitochondrial damage; but once the stressor persists they are thought to act as inducers of further impairments and loss of neuronal functions. Therefore, here we provide a brief overview of the current knowledge about the central role of cofilin/actin rods formation, where its dysregulation and malfunction might be the trigger to neurodegeneration.